title: Predictors of increased cumulative serum levels of the N-terminal prohormone of brain natriuretic peptide 4 days after acute spontaneous subarachnoid hemorrhage.
abstract: OBJECTIVE
  The rupture of an intracranial aneurysm is followed by increased intracranial pressure and decreased cerebral blood flow. A major systemic stress reaction follows, presumably to restore cerebral blood flow. However, this reaction can also cause adverse effects, including myocardial abnormalities, which are common and can be serious, and increased levels of natriuretic peptides, especially brain natriuretic peptide (BNP). The association of BNP with fluid and salt balance, vasospasm, brain ischemia, and cardiac injury has been studied but almost exclusively regarding events after admission. Brain natriuretic peptide has also been measured at various time points and analyzed in different ways statistically. The authors approached BNP measurement in a new way; they used the calculated area under the curve (AUC) for the first 4 days to quantitatively measure the BNP load during the first critical part of the disease state. Their rationale was a suspicion that early BNP load is a marker of the severity of the ictus and will influence the subsequent course of the disease by disturbing the fluid and salt balance.
  
  
  METHODS
  The study included 156 patients with acute spontaneous subarachnoid hemorrhage (SAH). Mean patient age was 59.8 ± 11.2 years, and 105 (67%) of the patients were female. An aneurysm was found in 138 patients. A total of 82 aneurysms were treated by endovascular coiling, 50 were treated by surgery, and 6 were untreated. At the time of admission, serum samples were collected for troponin-I analysis and for the N-terminal prohormone of BNP (NT-proBNP); daily thereafter, samples were collected for the NT-proBNP analysis. The cumulative BNP load was calculated as the AUC for NT-proBNP during the first 4 days. The following variables were studied in terms of their influence on the AUC for NT-proBNP: sex, age, World Federation of Neurosurgical Societies grade of SAH, Fisher grade, angiographic result, treatment of aneurysm, clinical neurological deterioration, verified infections, vasospasm treatment, and 6-month outcome.
  
  
  RESULTS
  The AUC for NT-proBNP was larger when variables indicated a more severe SAH. These variables were higher Fisher and World Federation of Neurosurgical Societies grades, high levels of troponin-I at admission, an aneurysm, neurological deficits, and infections. The AUC for NT-proBNP was also larger among women, older patients, and patients with poor outcomes. Linear regression showed that the best predicting model for large AUC for NT-proBNP was the combination of the following: female sex, high levels of troponin-I, an aneurysm, neurological deficits, and advanced age.
  
  
  CONCLUSIONS
  The cumulative BNP load during the first days after SAH can be predicted by variables describing the severity of the disease already known at the time of admission. This information can be used to identify patients at risk for an adverse course of the disease.
authors.affiliation: Department of Neuroscience, Section of Neurosurgery, and.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Nyberg
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Karlsson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ronne-Engström
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D012307:Risk Factors; D012422:Rupture, Spontaneous; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D013997:Time Factors; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain